Centrifugal rotor and method for using the same for delivering biological sample

ABSTRACT

Disclosed herein is a centrifugal rotor for delivering and analyzing biological sample. Chambers within the centrifugal rotor is used to split a biological sample, which comprises biological cellular components and biological fluids, into separate parts under centrifugal force after the biological sample being diluted, metered and distributed by the centrifugal rotor.

BACKGROUND

1. Field of Invention

The present invention relates to generally to devices and methods fordelivering and/or analyzing biological sample. More particularly, thepresent invention relates to a centrifugal rotor for delivering andanalyzing biological sample.

2. Description of Related Art

Biological tests of blood plasma and other biological fluids frequentlyrequire that fluids be quickly divided into predetermined volumes foranalysis in a variety of tests or assays. It is also frequentlydesirable to separate potentially interfering cellular components of thematerial from the biological fluid prior to testing. Such measurementand separation steps have previously been typically performed bycentrifugation to separate, for instance, blood plasma from the cellularcomponents, followed by manual or automated pipetting of predeterminedvolumes of the blood plasma into separate test wells. Such proceduresare labor intensive and time-consuming. As a result, various automatedsystems and methods have been proposed for providing multiple aliquotsof plasma suitable for testing in a more efficient manner.

A major advance in the analysis of biological fluids has been the use ofcentrifugal rotors. These rotors are designed to measure volumes of abiological fluid, such as blood, remove cellular components, and mix thefluid with an appropriate diluent for optical testing. Typically, therotors provide a plurality of discrete volumes of sample in separatecuvettes in which the sample is optically analyzed.

The rotors capable of performing these functions should be capable ofmeasuring and distributing relatively small volumes of liquid to a largenumber of cuvettes. The rotor design should be simple and amenable tolow-cost manufacturing procedures. In particular, it is desirable forthe rotors to be of unitary construction with no separable or movableparts. The present invention addresses these and other needs.

SUMMARY

In accordance with an aspect of the present invention, a centrifugalrotor includes a rotor body, which includes a sample applicationchamber, a diluent container, a mixing chamber, a distribution ring, atleast one splitting cuvette and a react cuvette. The diluent containerincludes a diluent inside thereof. The mixing chamber is disposedradially outward from the sample application chamber and the diluentcontainer for receiving fluid from thereof. The distribution ring isdisposed radially outward from the mixing chamber and connected with themixing chamber via a first siphon. The splitting cuvette is disposedradially outward from the distribution ring. Each splitting cuvetteincludes a relatively shallow cuvette and a relatively deep cuvettedisposed radially outward from the relatively shallow cuvette. The reactcuvette is connected with the relatively shallow cuvette via a secondsiphon.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a first delivery channel and a second delivery channel.The first delivery channel is interconnected between the second meteringchamber and the application sample chamber for removing a sample fluidin the application sample chamber under centrifugal force. The seconddelivery channel is interconnected between the second metering chamberand the mixing chamber for removing the sample fluid in the secondmetering chamber under centrifugal force. The first delivery channelcomprises a bubble-enhanced valve, a sacrificed valve, or a valve havinga cross-section smaller than a cross-section of the second meteringchamber and the application sample chamber. The second delivery channelcomprises a bubble-enhanced valve, a sacrificed valve or a valve havinga cross-section smaller than a cross-section of the second meteringchamber and the mixing chamber.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a third delivery channel interconnected between thediluent container and mixing chamber for removing a diluent in thediluent container under centrifugal force, wherein the third deliverychannel includes a bubble-enhanced valve or sacrificed valve.

According to another embodiment disclosed herein, the diluent containeris a piston-regulated chamber.

According to another embodiment disclosed herein, the diluent containeris an aluminum sealed diluent container.

According to another embodiment disclosed herein, the distribution ringincludes two opposite first end and second end, the first end isconnected to the first siphon, the second end is connected to the excessfluid dump, and the second end is radially outward from the first end.

According to another embodiment disclosed herein, the distribution ringis an arc with a corresponding center different from a center of therotor body.

In accordance with still another aspect of the present invention, amethod for using a centrifugal rotor to delivering a biological sampleincludes the step of using. chambers within single one centrifugal rotorto split a biological sample, which comprises biological cellularcomponents and biological fluids, into separate parts under centrifugalforce after the biological sample being diluted, metered and distributedby the single one centrifugal rotor.

According to an embodiment disclosed herein, the method further includesthe step of using a distribution ring within the single one centrifugalrotor to distribute the biological sample into a plurality of spilttingcuvettes, which are disposed radially outward from the distributionring.

According to another embodiment disclosed herein, the method furtherincludes the step of using a mixing chamber, which is disposed radiallyinward from the distribution ring, within the single one centrifugalrotor to dilute the biological sample.

According to another embodiment disclosed herein, the method furtherincludes the step of using the spiltting cuvette, which comprises arelatively shallow cuvette and a relatively deep cuvette disposedradially outward from the relatively shallow cuvette, so as to split thebiological sample into separate parts under centrifugal force.

According to another embodiment disclosed herein, the method furtherincludes the step of using a metering channel, which is interconnectedbetween the distribution ring and the spiltting cuvette, within thesingle one centrifugal rotor to meter the diluted biological sample.

According to another embodiment disclosed herein, the method furtherincludes the step of using a first metering chamber, which isinterconnected between the mixing chamber and the distribution ring, tometer the diluted biological sample.

In accordance with another aspect of the present invention, acentrifugal rotor includes a rotor body, which includes a sampleapplication chamber, a diluent container, a mixing and splittingchamber, a distribution ring, a first metering chamber, a secondmetering chamber, a first excess dump and at least one cuvette. Themixing and splitting chamber is disposed radially outward from thesample application chamber and the diluent container for receiving fluidfrom thereof. The first metering chamber is interconnected between themixing and splitting chamber and the sample application chamber. Thesecond metering chamber is disposed radially outward from and connectedwith the first metering chamber. The first excess dump is connected withthe second metering chamber. The distribution ring is disposed radiallyoutward from the mixing and splitting chamber, and connected with themixing and splitting chamber via a first siphon. The at least one reactcuvette is disposed radially outward from and connected with thedistribution ring.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a metering channel interconnected between thedistribution ring and the react cuvette.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a valve interconnected between the metering channel andthe react cuvette, wherein the valve is a bubble-enhanced valve, asacrificed valve or a valve having a cross-section smaller than across-section of the metering channel and the react cuvette.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a second excess fluid dump, wherein the distributionring is interconnected between the first siphon and the second excessfluid dump.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a first delivery channel and a second delivery channel.The first delivery channel is interconnected between the first meteringchamber and the mixing and splitting chamber for removing a fluid in thefirst metering chamber under centrifugal force. The second deliverychannel is interconnected between the diluent container and the mixingand splitting chamber for removing a diluent in the diluent containerunder centrifugal force. The first delivery channel comprises abubble-enhanced valve, a sacrificed valve or a valve having across-section smaller than a cross-section of the first metering chamberand the mixing and splitting chamber. The second delivery channelcomprises a sacrificed valve, a bubble-enhanced valve or a valve havinga cross-section smaller than a cross-section of the diluent containerand the mixing and splitting chamber.

According to another embodiment disclosed herein, the mixing andsplitting chamber includes a chamber tail disposed radially outward fromthereof.

According to another embodiment disclosed herein, the chamber tail is arelatively deeper area compared with the remaining area of the mixingand splitting chamber.

According to another embodiment disclosed herein, the diluent containeris a piston-regulated chamber.

According to another embodiment disclosed herein, the diluent containeris an aluminum sealed diluent container.

According to another embodiment disclosed herein, the distribution ringincludes two opposite first end and second end, the first end isconnected to the first siphon, the second end is connected to the secondexcess fluid dump, and the second end is radially outward from the firstend.

According to another embodiment disclosed herein, the distribution ringis an arc with a corresponding center different from a center of therotor body.

According to another embodiment disclosed herein, the distribution ringis part of a circle, which is concentric to a circumference of the rotorbody.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes at least one splitting cuvette disposed radiallyoutward from the distribution ring. The splitting cuvette includes arelatively shallow cuvette and a relatively deep cuvette disposedradially outward from the relatively shallow cuvette.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a metering channel interconnected between thedistribution ring and the splitting cuvette.

According to another embodiment disclosed herein, the centrifugal rotorfurther includes a valve interconnected between the metering channel andthe splitting cuvette, wherein the valve is a bubble-enhanced valve, asacrificed valve or a valve having a cross-section smaller than across-section of the metering channel and the splitting cuvette.

According to another embodiment disclosed herein, the spiltting cuvettefurther comprises a neck, which has a smaller cross-sectional area thanthe relatively shallow cuvette and relatively deep cuvette has,interconnected between the relatively shallow cuvette and relativelydeep cuvette.

It is to be understood that both the foregoing general description andthe following detailed description are by examples, and are intended toprovide further explanation of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are included to provide a furtherunderstanding of the invention, and are incorporated in and constitute apart of this specification. The drawings illustrate embodiments of theinvention and, together with the description, serve to explain theprinciples of the invention. In the drawings,

FIG. 1 illustrates a perspective view of a centrifugal rotor accordingto one embodiment of this invention;

FIG. 2 illustrates a plan view of the centrifugal rotor in FIG. 1;

FIG. 3 illustrates a plan view of a centrifugal rotor according toanother embodiment of this invention;

FIG. 4 illustrates a perspective view of a centrifugal rotor accordingto still another embodiment of this invention;

FIG. 5 illustrates a plan view of the centrifugal rotor in FIG. 4; and

FIG. 6 illustrates a plan view of a centrifugal rotor according to stillanother embodiment of this invention;

FIG. 7 illustrates a plan view of a centrifugal rotor according to stillanother embodiment of this invention;

FIGS. 8 and 9 illustrate two examples of the diluent container asillustrated in FIG. 7;

FIG. 10 illustrates a plan view of a centrifugal rotor according tostill another embodiment of this invention; and

FIGS. 11 and 12 illustrate two examples of the bubble-enhanced valve asillustrated in FIG. 10.

DESCRIPTION OF THE EMBODIMENTS

Reference will now be made in detail to the present embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers are used in thedrawings and the description to refer to the same or like parts.

Referring FIG. 1 and FIG. 2, which respectively illustrate a perspectiveview and plan view of a centrifugal rotor according to one embodiment ofthis invention. The centrifugal rotor 100 includes a rotor body 101,e.g. a solid disk, to be used under centrifugal force, e.g. mounted in acentrifuge. There are several chambers designed within the rotor body101 for delivering and/or analyzing biological samples, e.g. blood,urine, spinal fluid, semen and etc. In particular, a sample applicationchamber 106 and a diluent container 104 are designed closer to a center101 a of the rotor body 101 than the remaining chambers or cuvettes. Apredetermined volume of diluents 114 b (as illustrated in FIG. 2) can bepre-stored inside the diluent container 104. The biological sample, e.g.blood, can be manually deposited into the sample application chamber106. A mixing chamber 108 is positioned radially outward from the sampleapplication chamber 104 and the diluent container 106 such that themixing chamber 108 is able to receive fluid from thereof undercentrifugal force. A delivery channel 106 a is interconnected betweenthe sample application chamber 106 and the mixing chamber 108 forremoving a fluid in the sample application chamber 106 under centrifugalforce. Another delivery channel 104 a is interconnected between thediluent container 104 and the mixing chamber 108 for removing a diluentin the diluent container 104 under centrifugal force. A distributionring 110 is positioned radially outward from the mixing chamber 108 andconnected with the mixing chamber 108 via a siphon 108 a. After thebiological sample, e.g. blood, and diluent are mixed in the mixingchamber 108, the rotor body 101 is stopped, i.e. no centrifugal force isapplied, and the siphon 108 a is primed to deliver the dilutedbiological sample to the distribution ring 110. In this embodiment, thedistribution ring 110 is part of a circle, which is concentric to acircumference of the rotor body 101. That is, the distribution ring 110and circumference of the rotor body 101 share a common center 101 a.

At least one analysis unit 114 is arranged radially outward from thedistribution ring 110. Each analysis unit 114 includes a splittingcuvette 114 b and a react cuvette 114 c. A metering channel 114 a isinterconnected between the distribution ring 110 and the spilttingcuvette 114 b. When the rotor body 101 is applied with a centrifugalforce again, the distribution ring 110 distributes the dilutedbiological sample into each metering channel 114 a first and leaves therest into an excess fluid dump 112. A proper centrifugal force should beapplied not to enable the biological sample in each metering channel 114a to penetrate through a valve 114 e, i.e. a portion with smallercross-sectional area, between each metering channel 114 a and eachsplitting cuvette 114 b.

Each splitting cuvette 114 b can be further divided into three parts: arelatively shallow cuvette 114 b ₁, relatively deep cuvette 114 b ₂ anda neck 114 b ₃ between thereof. The relatively deep cuvette 114 b ₂ ispositioned radially outward from the relatively shallow cuvette 114 b ₁.The neck 114 b ₃ has a smaller cross-sectional area than the relativelyshallow cuvette 114 b ₁ and relatively deep cuvette 114 b ₂ has. When aproper centrifugal force is applied to the rotor body 101, a relativelyheavy part of the biological sample, e.g. blood cells of the wholeblood, can be deliver through the neck 114 b ₃ and trapped within therelatively deep cuvette 114 b ₂. The react cuvette 114 c is connectedwith the relatively shallow cuvette 114 b ₁ or the relatively deepcuvette 114 b ₂ via a siphon 114 d. A desired reagent may bepre-deposited within the react cuvette 114 c for performing a desiredbiological analysis. In an alternate embodiment, the splitting cuvette114 b as illustrated in FIG. 1 can be replaced by the splitting cuvette214 a as illustrated in FIG. 4.

Referring to FIG. 3, which illustrates a plan view of a centrifugalrotor according to another embodiment of this invention. This embodimentis slightly different from the embodiment illustrated in FIG. 2 in thatthe distribution ring 110 a is gradually radially outward from thedistribution ring 110 of FIG. 2, from the end, connected to the siphon108 a, to the end, connected to the excess fluid dump 112. That is, thedistribution ring 110 a has the end, which is connected to the excessfluid dump 112, arranged radially outward from the other end, which isconnected to the siphon 108 a. In this embodiment, the distribution ring110 a is an arc with its corresponding center 101 b different from thecenter 101 a, which is a center of the distribution ring 110 and therotor body 101. Besides, the distribution ring 110 a is equipped with alarger radius than a radius of the distribution ring 110.

This design of the distribution ring is to avoid “trapping the samplewithin the distribution ring”, thereby effectively routing excess sampleinto the excess dump. “The sample trapped within the distribution ring”may result in cosstalk between adjacent analysis units, splittingcuvettes or react cuvettes, e.g. reactant in a cuvette diffuses intoanother cuvette via the sample trapped within the distribution ring. Thesame design of the distribution ring can also be applied to otherembodiments of this disclosure.

Referring FIG. 4 and FIG. 5, which respectively illustrate a perspectiveview and a plan view of a centrifugal rotor according to still anotherembodiment of this invention. The centrifugal rotor 200 includes a rotorbody 201, e.g. a solid disk, to be used under centrifugal force, e.g.mounted in a centrifuge. There are several chambers designed within therotor body 201 for delivering and/or analyzing biological samples, e.g.blood, urine, spinal fluid, semen and etc. In particular, a sampleapplication chamber 206 and a diluent container 204 are designed closerto a center 201 a of the rotor body 201 than the remaining chambers orcuvettes. A predetermined volume of diluents can be pre-stored insidethe diluent container 204. The biological sample, e.g. blood, can bemanually deposited into the sample application chamber 206. A mixingchamber 208 is positioned radially outward from the sample applicationchamber 204 and the diluent container 206 such that the mixing chamber208 is able to receive fluid from thereof under centrifugal force. Adelivery channel 206 a is interconnected between the sample applicationchamber 206 and the mixing chamber 208 for removing a fluid in thesample application chamber 206 under centrifugal force. Another deliverychannel 204 a is interconnected between the diluent container 204 andthe mixing chamber 208 for removing a diluent in the diluent container204 under centrifugal force. A distribution ring 210 is positionedradially outward from the mixing chamber 208. A metering chamber 209 isinterconnected between the mixing chamber 208 and the distribution ring210. The metering chamber 209 is equipped with an excess fluid dump 209a. A siphon 208 a is interconnected between the mixing chamber 208 andmetering chamber 209. Another siphon 209 b is interconnected between thedistribution ring 210 and metering chamber 209. After the biologicalsample, e.g. blood, and diluent are mixed in the mixing chamber 208, therotor body 201 is stopped, i.e. no centrifugal force is applied, and thesiphon 208 a is primed to deliver the diluted biological sample to themetering chamber 209. The rotor body 201 is then rotated again to metera desired volume of the diluted biological sample and leave the rest tothe excess fluid dump 209 a. After the diluted biological sample ismetered in the metering chamber 209, the rotor body 201 is stoppedagain, and the siphon 209 b is primed to deliver the metered biologicalsample 209 c to the distribution ring 210.

At least one analysis unit 214 is designed radially outward from thedistribution ring 210. Each analysis unit 214 includes a splittingcuvette 214 a and a react cuvette 214 b. Since the desired volume of thediluted biological sample has been pre-metered before entering into thedistribution ring 210, a metering channel, e.g. 114 a in FIG. 2, may notbe necessary in this embodiment. When the rotor body 201 is applied witha centrifugal force again, the distribution ring 210 distributes thediluted and metered biological sample into each splitting cuvette 214 a.

Each splitting cuvette 214 a can be further divided into two parts: arelatively shallow cuvette 214 a ₁ and a relatively deep cuvette 214 a₂. The relatively deep cuvette 214 a ₂ is positioned radially outwardfrom the relatively shallow cuvette 214 a ₂. When a proper centrifugalforce is applied to the rotor body 201, a relatively heavy part of thebiological sample, e.g. blood cells of the whole blood, can be movedinto and trapped within the relatively deep cuvette 214 a ₂. The reactcuvette 214 b is connected with the relatively shallow cuvette 214 a ₁or the relatively deep cuvette 214 a ₂ via a siphon 214 c. A desiredreagent may be pre-deposited within the react cuvette 214 b forperforming a desired biological analysis. In an alternate embodiment,the splitting cuvette 214 a as illustrated in FIG. 4 can be replaced bythe splitting cuvette 114 b as illustrated in FIG. 1.

Referring to FIG. 6, which illustrates a plan view of a centrifugalrotor according to still another embodiment of this invention. Thisembodiment is slightly different from the embodiment illustrated in FIG.5 in that another metering chamber 207 is interconnected between themixing chamber 208 and the sample application chamber 206. The meteringchamber 207 is also equipped with an excess fluid dump 207 a (using adelivery channel 207 c to interconnect between thereof). A deliverychannel 206 a is interconnected between the metering chamber 207 and theapplication sample chamber 206 for removing a sample fluid in theapplication sample chamber 206 under centrifugal force. A deliverychannel 207 b is interconnected between the metering chamber 207 and themixing chamber 208 for removing the sample fluid in the metering chamber207 under centrifugal force. In this embodiment, the delivery channel206 a has a larger cross-sectional area than the delivery channel 207 bhas, and the delivery channel 207 c has a larger cross-sectional areathan the delivery channel 207 b has Therefore, when a proper centrifugalforce is applied to the rotor body 201′, the biological sample can bemetered in the metering chamber 207 before entering into the mixingchamber 208. Besides, the delivery channel 206 a has a largercross-sectional area than the delivery channel 204 a has. Thus, if aproper centrifugal force is applied to the rotor body 201′, the diluentin the diluent container 204 does not enter into the mixing chamber 208when the biological sample enters into the metering chamber 207. Themetering chamber 207 is designed to meter a desired volume of theundiluted biological sample so as to control a mixed ratio of thebiological sample and diluent, which is pre-stored in the diluentcontainer 204.

Referring to FIG. 7, which illustrates a plan view of a centrifugalrotor according to still another embodiment of this invention. Thecentrifugal rotor 300 includes a rotor body 301, e.g. a solid disk, tobe used under centrifugal force, e.g. mounted in a centrifuge. There areseveral chambers designed within the rotor body 301 for deliveringand/or analyzing biological samples, e.g. blood, urine, spinal fluid,semen and etc. In particular, a sample application chamber 306 (equippedwith a sample filling opening 306 a) and a diluent container 304 aredesigned closer to a center of the rotor body 301 than the remainingchambers or cuvettes. The biological sample, e.g. blood, can be manuallydeposited into the sample application chamber 306 through the samplefilling opening 306 a. A metering chamber 307 is positioned radiallyoutward from the sample application chamber 306 to pre-measure thesample, e.g. whole blood, before entering a mixing and splitting chamber308. Excess sample is routed to a metering chamber 305 and an excessdump 305 a when a centrifugal force is applied. The mixing and splittingchamber 308 is positioned radially outward from the sample applicationchamber 304 and the diluent container 306 such that the mixing andsplitting chamber 308 is able to receive fluid from thereof undercentrifugal force. The mixing and splitting chamber 308 performs both“mixing the sample with the diluent” and “splitting the diluted sampleinto two parts”. A relatively heavier part of the diluted sample, e.g.blood cells of the whole blood, will be routed to and trapped within achamber tail 308 a, e.g. a relatively deeper area compared with theremaining area of the mixing and splitting chamber, under centrifugalforce. A distribution ring 310 is positioned radially outward from themixing and splitting chamber 308 and connected with the mixing andsplitting chamber 308 via a siphon 308 b. After the biological sample,e.g. blood, and diluent are mixed and split in the mixing and splittingchamber 308, the rotor body 301 is stopped, i.e. no centrifugal force isapplied, and the siphon 308 b is primed to deliver a relatively lighterpart of the diluted sample, e.g. diluted plasma of the whole blood, tothe distribution ring 310. With the mixing and splitting chamber 308,the sample can be effectively used with the less sample wasted (comparedwith the mixing function and splitting function are executed by twoseparate chambers). For example, if 35 μl whole blood is split first andthen mixed with 500 μl diluent by two separate chambers, only about 17μl blood plasma can be extracted. Deducting the volume wasted in siphonand splitting chamber (about 4 μl), only 13 μl blood plasma can beeffectively used. With the mixing and splitting chamber 308, 35 μl wholeblood plus 500 μl diluent are mixed and split in the same chamber, only4 μl diluted blood wasted in siphon and splitting chamber. Morepercentage of 35 μl whole blood can be effectively used. Thedistribution ring 310 has two ends to be respectively connected with thesiphon 308 b and an excess dump 309. A plurality of react cuvettes 314are positioned radially outward from and connected with the distributionring 310. When the rotor body 301 is applied with a centrifugal forceagain, the distribution ring 310 distributes the relatively lighter partof the diluted sample into each react cuvette 314 first and leaves therest into the excess fluid dump 309. The distribution ring 310 may beequipped a vent hole 311, and a vent channel is interconnected betweenthe vent hole 311 and the distribution ring 310.

In an alternate embodiment, the react cuvette 314 can be replaced by theanalysis unit 114 as illustrated in FIG. 1, the analysis unit 214 asillustrated in FIG. 4, or the analysis units (414, 415) as illustratedin FIG. 10.

FIGS. 8 and 9 illustrate cross-sectional views of two examples of thediluent container as illustrated in FIG. 7. FIG. 8 illustrates apiston-regulated diluent container 304 with two pistons (304 b and 304c) movably sealing the chamber, thereby sealing the diluent underthereof. When a force applied to the piston 304 b, the piston 304 b ismoved downwards (illustrated as 304 b′) while the piston 304 c is movedupwards (illustrated as 304 c′). Therefore, the diluent can be flowedout through a channel 304 a. FIG. 8 illustrates the diluent container304 equipped with an extra aluminum sealed diluent container 304 d. Thealuminum sealed diluent container 304 d is vertically slidable withinthe diluent container 304. When a force applied to the diluent container304 d, the diluent container 304 d is moved downwards and its aluminumseal 304 e can be broken by a convex member 304 f. Therefore, thediluent can be flowed out of the diluent container 304 d and routed tothe mixing and splitting chamber through the channel 304 a.

Referring to FIG. 10, which illustrates a plan view of a centrifugalrotor according to still another embodiment of this invention. Thecentrifugal rotor 400 includes a rotor body 401, e.g. a solid disk, tobe used under centrifugal force, e.g. mounted in a centrifuge. There areseveral chambers designed within the rotor body 401 for deliveringand/or analyzing biological samples, e.g. blood, urine, spinal fluid,semen and etc. In particular, a sample application chamber 406 and adiluent container 404 are designed closer to a center of the rotor body401 than the remaining chambers or cuvettes. A metering chamber 407 isinterconnected between a mixing chamber 408 and the sample applicationchamber 406. The metering chamber 407 is also equipped with an excessfluid dump 407 a (using a delivery channel to interconnect betweenthereof). This embodiment is different from the above-discussedembodiments in that the delivery channel between chambers is equippedwith a bubble-enhanced valve or sacrificed valve. For example, adelivery channel 404 a has a sacrificed valve, which has a removablesolid block within the delivery channel to be removed by a user. Whenthe solid block is removed, the delivery channel 404 a becomes a normaldelivery channel. For example, a delivery channel 407 b has abubble-enhanced valve. By “bubble-enhanced valve”, it means “a valve ofa shape to trap a bubble within the delivery channel when a liquid flowpasses by, wherein the bubble is able to regulate the flow rate of thedelivery channel”.

The distribution ring 410 has two ends to be respectively connected withthe siphon 408 b and an excess dump 409. Two types of analysis units(414, 415) are positioned radially outward from and connected with thedistribution ring 410. When the rotor body 401 is applied with acentrifugal force again, the distribution ring 410 distributes thediluted sample into each analysis unit (414, 415) first and leaves therest into the excess fluid dump 409. The analysis unit 415 is almost thesame as the design of the analysis unit 114 as illustrated in FIG. 1 andFIG. 2 except some shape variants. The analysis unit 414 includes asplitting cuvette and a react cuvette 414 d. The splitting cuvetteincludes a metering channel 414 a, a cuvette 414 b and a bubble-enhancedvalve 414 c interconnected therebetween. When the rotor body 301 isapplied with a centrifugal force, the relatively lighter part of thediluted sample will be routed to the cuvette 414 b and further routed tothe react cuvette 414 d for a desirable reaction.

FIGS. 11 and 12 illustrate two examples of the bubble-enhanced valve asillustrated in FIG. 10. The bubble-enhanced valve 414 c ₁ includes deadareas, where air can be easily trapped to form bubbles, and the bubbles417 tend to regulate the flow rate of the passing liquid, i.e. slow orstop the flow rate of the passing liquid. The bubble-enhanced valve 414c ₂ includes widened channel to create dead areas, where air can beeasily trapped to form bubbles, and the bubbles 418 tend to regulate theflow rate of the passing liquid, i.e. slow or stop the flow rate of thepassing liquid. The bubble-enhanced valve should be functioned alongwith a centrifugal force to control the passing liquid through adelivery channel.

According to the above-discussed embodiment, the centrifugal rotorattempts to split a biological sample, which comprises biologicalcellular components and biological fluids, into separate parts undercentrifugal force after the biological sample being diluted, metered anddistributed. An advantage to design such centrifugal rotor is to reducea required volume of a biological sample to be filled into the sampleapplication chamber. Another advantage to design such centrifugal rotoris to allow a relatively larger tolerance for actual size's precision ofchambers such that the centrifugal rotor is amenable to low-costmanufacturing procedures.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the structure of the presentinvention without departing from the scope or spirit of the invention.In view of the foregoing, it is intended that the present inventioncover modifications and variations of this invention provided they fallwithin the scope of the following claims and their equivalents.

1. A centrifugal rotor comprising: a rotor body comprising: a sampleapplication chamber; a diluent container comprising diluents insidethereof; a mixing chamber disposed radially outward from the sampleapplication chamber and the diluent container for receiving fluid fromthereof; a distribution ring disposed radially outward from the mixingchamber and connected with the mixing chamber via a first siphon; atleast one splitting cuvette disposed radially outward from thedistribution ring, the splitting cuvette comprising: a relativelyshallow cuvette; and a relatively deep cuvette disposed radially outwardfrom the relatively shallow cuvette; and a react cuvette connected withthe relatively shallow cuvette via a second siphon.
 2. The centrifugalrotor of claim 1, further comprising a metering channel interconnectedbetween the distribution ring and the splitting cuvette.
 3. Thecentrifugal rotor of claim 2, further comprising a valve interconnectedbetween the metering channel and the splitting cuvette, wherein thevalve is a bubble-enhanced valve, a sacrificed valve or a valve having across-section smaller than a cross-section of the metering channel andthe splitting cuvette.
 4. The centrifugal rotor of claim 1, furthercomprising an excess fluid dump, wherein the distribution ring isinterconnected between the first siphon and the excess fluid dump. 5.The centrifugal rotor of claim 1, wherein the spiltting cuvette furthercomprises a neck, which has a smaller cross-sectional area than therelatively shallow cuvette and relatively deep cuvette has and isinterconnected between the relatively shallow cuvette and relativelydeep cuvette.
 6. The centrifugal rotor of claim 1, further comprising: afirst delivery channel interconnected between the sample applicationchamber and mixing chamber for removing a fluid in the sampleapplication chamber under centrifugal force; and a second deliverychannel interconnected between the diluent container and mixing chamberfor removing a diluent in the diluent container under centrifugal force,wherein the first delivery channel comprises a bubble-enhanced valve, asacrificed valve or a valve having a cross-section smaller than across-section of the sample application chamber and mixing chamber, andthe second delivery channel comprises a sacrificed valve, abubble-enhanced valve or a valve having a cross-section smaller than across-section of the diluent container and mixing chamber.
 7. Thecentrifugal rotor of claim 1, further comprising: a first meteringchamber interconnected between the mixing chamber and the distributionring; and a first excess fluid dump connected with the first meteringchamber.
 8. The centrifugal rotor of claim 7, wherein the first meteringchamber is connected with the mixing chamber via a third siphon, andconnected with the distribution ring via a fourth siphon.
 9. Thecentrifugal rotor of claim 7, further comprising: a second meteringchamber interconnected between the mixing chamber and the sampleapplication chamber; and a second excess fluid dump connected with thesecond metering chamber.
 10. The centrifugal rotor of claim 9, furthercomprising: a first delivery channel interconnected between the secondmetering chamber and the application sample chamber for removing asample fluid in the application sample chamber under centrifugal force;and a second delivery channel interconnected between the second meteringchamber and the mixing chamber for removing the sample fluid in thesecond metering chamber under centrifugal force, wherein the firstdelivery channel comprises a bubble-enhanced valve, a sacrificed valve,or a valve having a cross-section smaller than a cross-section of thesecond metering chamber and the application sample chamber, and thesecond delivery channel comprises a bubble-enhanced valve, a sacrificedvalve or a valve having a cross-section smaller than a cross-section ofthe second metering chamber and the mixing chamber.
 11. The centrifugalrotor of claim 10, further comprising: a third delivery channelinterconnected between the diluent container and mixing chamber forremoving a diluent in the diluent container under centrifugal force,wherein the third delivery channel comprises a bubble-enhanced valve, asacrificed valve or a valve having a cross-section smaller than across-section of the diluent container and the mixing chamber.
 12. Thecentrifugal rotor of claim 1, wherein the diluent container is apiston-regulated chamber.
 13. The centrifugal rotor of claim 1, whereinthe diluent container is an aluminum sealed diluent container.
 14. Thecentrifugal rotor of claim 1, wherein the distribution ring comprisestwo opposite first end and second end, the first end is connected to thefirst siphon, the second end is connected to the excess fluid dump, thesecond end is radially outward from the first end.
 15. The centrifugalrotor of claim 13, wherein the distribution ring is an arc with acorresponding center different from a center of the rotor body.
 16. Amethod for using a centrifugal rotor to deliver a biological samplecomprising: using chambers within single one centrifugal rotor to splita biological sample, which comprises biological cellular components andbiological fluids, into separate parts under centrifugal force after thebiological sample being diluted, metered and distributed by the singleone centrifugal rotor.
 17. The method of claim 16, further comprising:using a distribution ring within the single one centrifugal rotor todistribute the biological sample into a plurality of spiltting cuvettes,which are disposed radially outward from the distribution ring.
 18. Themethod of claim 17, further comprising: using a mixing chamber, which isdisposed radially inward from the distribution ring, within the singleone centrifugal rotor to dilute the biological sample.
 19. The method ofclaim 18, further comprising: using the spiltting cuvette, whichcomprises a relatively shallow cuvette and a relatively deep cuvettedisposed radially outward from the relatively shallow cuvette, so as tosplit the biological sample into separate parts under centrifugal force.20. The method of claim 19, further comprising: using a meteringchannel, which is interconnected between the distribution ring and thespiltting cuvette, within the single one centrifugal rotor to meter thediluted biological sample.
 21. The method of claim 19, furthercomprising: using a first metering chamber, which is interconnectedbetween the mixing chamber and the distribution ring, to meter thediluted biological sample.
 22. The method of claim 21, furthercomprising: using a second metering chamber, which is interconnectedbetween the mixing chamber and the sample application chamber, to meterthe undiluted biological sample.
 23. A centrifugal rotor comprising: arotor body comprising: a sample application chamber; a diluent containercomprising diluents inside thereof; a mixing and splitting chamberdisposed radially outward from the sample application chamber and thediluent container for receiving fluid from thereof; a first meteringchamber interconnected between the mixing and splitting chamber and thesample application chamber; a second metering chamber disposed radiallyoutward from and connected with the first metering chamber; a firstexcess dump connected with the second metering chamber; a distributionring disposed radially outward from the mixing and splitting chamber,and connected with the mixing and splitting chamber via a first siphon;and at least one react cuvette disposed radially outward from andconnected with the distribution ring.
 24. The centrifugal rotor of claim23, further comprising a metering channel interconnected between thedistribution ring and the react cuvette.
 25. The centrifugal rotor ofclaim 24, further comprising a valve interconnected between the meteringchannel and the react cuvette, wherein the valve is a bubble-enhancedvalve, a sacrificed valve or a valve having a cross-section smaller thana cross-section of the metering channel and the react cuvette.
 26. Thecentrifugal rotor of claim 23, further comprising a second excess fluiddump, wherein the distribution ring is interconnected between the firstsiphon and the second excess fluid dump.
 27. The centrifugal rotor ofclaim 23, further comprising: a first delivery channel interconnectedbetween the first metering chamber and the mixing and splitting chamberfor removing a fluid in the first metering chamber under centrifugalforce; and a second delivery channel interconnected between the diluentcontainer and the mixing and splitting chamber for removing a diluent inthe diluent container under centrifugal force, wherein the firstdelivery channel comprises a bubble-enhanced valve, a sacrificed valveor a valve having a cross-section smaller than a cross-section of thefirst metering chamber and the mixing and splitting chamber, and thesecond delivery channel comprises a sacrificed valve, a bubble-enhancedvalve or a valve having a cross-section smaller than a cross-section ofthe diluent container and the mixing and splitting chamber.
 28. Thecentrifugal rotor of claim 23, wherein the mixing and splitting chambercomprises a chamber tail disposed radially outward from thereof.
 29. Thecentrifugal rotor of claim 28, wherein the chamber tail is a relativelydeeper area compared with the remaining area of the mixing and splittingchamber.
 30. The centrifugal rotor of claim 23, wherein the diluentcontainer is a piston-regulated chamber.
 31. The centrifugal rotor ofclaim 23, wherein the diluent container is an aluminum sealed diluentcontainer.
 32. The centrifugal rotor of claim 23, wherein thedistribution ring comprises two opposite first end and second end, thefirst end is connected to the first siphon, the second end is connectedto the second excess fluid dump, the second end is radially outward fromthe first end.
 33. The centrifugal rotor of claim 32, wherein thedistribution ring is an arc with a corresponding center different from acenter of the rotor body.
 34. The centrifugal rotor of claim 23, whereinthe distribution ring is part of a circle, which is concentric to acircumference of the rotor body.
 35. The centrifugal rotor of claim 23,further comprising at least one splitting cuvette disposed radiallyoutward from the distribution ring, the splitting cuvette comprising: arelatively shallow cuvette; and a relatively deep cuvette disposedradially outward from the relatively shallow cuvette.
 36. Thecentrifugal rotor of claim 35, further comprising a metering channelinterconnected between the distribution ring and the splitting cuvette.37. The centrifugal rotor of claim 36, further comprising a valveinterconnected between the metering channel and the splitting cuvette,wherein the valve is a bubble-enhanced valve, a sacrificed valve or avalve having a cross-section smaller than a cross-section of themetering channel and the splitting cuvette.
 38. The centrifugal rotor ofclaim 37, wherein the spiltting cuvette further comprises a neck, whichhas a smaller cross-sectional area than the relatively shallow cuvetteand relatively deep cuvette has, interconnected between the relativelyshallow cuvette and relatively deep cuvette.